Sticky Patches on Lipid Nanoparticles Enable the Selective Targeting and Killing of Untargetable Cancer Cells
| Autor: | Charles Zhu, Michelle Sempkowski, Stavroula Sofou, Frank Bruchertseifer, Ioannis G. Kevrekidis, Monica Zofia Menzenski, Alfred Morgenstern |
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| Rok vydání: | 2016 |
| Předmět: |
Actinium
0301 basic medicine Cell Survival Receptor ErbB-2 Kinetics Cell Nanoparticle Breast Neoplasms Ligands Endocytosis 03 medical and health sciences Drug Delivery Systems 0302 clinical medicine Cell Line Tumor Electrochemistry medicine Humans Nanotechnology General Materials Science Receptor Spectroscopy Antibiotics Antineoplastic Chemistry Vesicle Surfaces and Interfaces Condensed Matter Physics Lipids Molecular biology 030104 developmental biology medicine.anatomical_structure Doxorubicin Cell culture 030220 oncology & carcinogenesis Cancer cell MCF-7 Cells Biophysics Nanoparticles Female |
| Zdroj: | Langmuir. 32:8329-8338 |
| ISSN: | 1520-5827 0743-7463 |
| Popis: | Effective targeting by uniformly functionalized nanoparticles is limited to cancer cells expressing at least two copies of targeted receptors per nanoparticle footprint (approximately ≥2 × 10(5) receptor copies per cell); such a receptor density supports the required multivalent interaction between the neighboring receptors and the ligands from a single nanoparticle. To enable selective targeting below this receptor density, ligands on the surface of lipid vesicles were displayed in clusters that were designed to form at the acidic pH of the tumor interstitium. Vesicles with clustered HER2-targeting peptides within such sticky patches (sticky vesicles) were compared to uniformly functionalized vesicles. On HER2-negative breast cancer cells MDA-MB-231 and MCF7 {expressing (8.3 ± 0.8) × 10(4) and (5.4 ± 0.9) × 10(4) HER2 copies per cell, respectively}, only the sticky vesicles exhibited detectable specific targeting (KD ≈ 49-69 nM); dissociation (0.005-0.009 min(-1)) and endocytosis rates (0.024-0.026 min(-1)) were independent of HER2 expression for these cells. MDA-MB-231 and MCF7 were killed only by sticky vesicles encapsulating doxorubicin (32-40% viability) or α-particle emitter (225)Ac (39-58% viability) and were not affected by uniformly functionalized vesicles (80% viability). Toxicities on cardiomyocytes and normal breast cells (expressing HER2 at considerably lower but not insignificant levels) were not observed, suggesting the potential of tunable clustered ligand display for the selective killing of cancer cells with low receptor densities. |
| Databáze: | OpenAIRE |
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